effects of inflammation on gingiva

1. Dr.D.Navya,MDS

2.  Inflammation: is defined as an observable alteration in
tissues associated with changes in vascular permeability
and dilation, often with the infiltration of leukocytes into
affected tissues.
 These changes result in the Erythema, Edema, Heat,
Pain, and loss of function being the cardinal signs of
inflammation
 Typically inflammation can progress through three
stages:
 Acute
 Sub-Acute and
 Chronic.

3.  The body responds to an infection by developing an
inflammatory response.
 Early work investigating gingival inflammation described
the progression from a state of health to a state of
inflammation and tissue loss and divided the progression
into four stages.
The gingiva is no exception, and inflammation in the
gingiva is termed gingivitis.

4. Gingival inflammation has two components:
Acute inflammatory component,
with vasodilation,
edema, and
polymorphonuclear infiltration, and the
Chronic inflammatory component,
 with B and T lymphocytes and
 capillary proliferation forming a granulomatous response.

5.  Each gingival region can have varying amounts of the acute
or chronic component.
 For patients in whom acute inflammatory changes
predominate, clinicians can expect a more dramatic
response to initial therapy,
 whereas for patients with the established or advanced
lesion in whom chronic inflammation and tissue damage
dominate, such a significant tissue response will not occur.
The more inflamed a gingival unit appears clinically, the better the
chances of therapeutic measures resulting in a return to normal gingival health.

6.  Pathologic changes in gingivitis are associated with the
presence of oral microorganisms attached to the tooth and
perhaps in or near the gingival sulcus.
 These organisms are capable of synthesizing products
(e.g., collagenase, hyaluronidase, protease, chondroitin
sulfatase, endotoxin) that cause damage to epithelial and
connective tissue cells, as well as to intercellular
constituents, such as collagen, ground substance, and
glycocalyx (cell coat).
 The resultant widening of the spaces between the junctional
epithelial cells during early gingivitis may permit injurious
agents derived from bacteria, or bacteria themselves, to
gain access to the connective tissue.

7.  Despite extensive research, we still cannot distinguish
definitively between normal gingival tissue and the initial
stage of gingivitis.
 Most biopsies of clinically normal human gingiva contain
inflammatory cells consisting predominantly of T cells, with
very few B cells or plasma cells.
 Under normal conditions, therefore, a constant stream of
neutrophils is migrating from the vessels of the gingival
plexus through the junctional epithelium, to the gingival
margin, and into the gingival sulcus and oral cavity.

8.  Pristine Gingiva: It is virtually impossible to obtain pristine or
noninfiltrated, histologically healthy gingival samples from
humans. Nonhuman experiments are therefore the major source
of material for the study of the temporal, histopathology
sequences from healthy gingiva to an advanced, destructive
lesion (periodontitis) (Page and Schroeder, 1976).
 Despite extensive research, we still cannot distinguish
definitively between normal gingival tissue and the gingivitis
in early stages. However the normal gingiva is characterized
by:

9.  Histologic characteristics of healthy
gingiva
Normal junctional epithelium
Few phagocytosing polymorphonudear cells from the
subepithelial vasculature in the junctional epithelium
Minimal exudates from the sulcus
Normal fibroblasts, connective tissue, collagen fibers, and
alveolar bone

10.  Little plaque accumulation
 Normal JE
 Few PMNs
 Dense Collagen Fibres
 Intact Fibroblasts

11. 1 Plaque present at gingival margin
2 Disease begins at the gingival margin
3 Change in gingival color
4 Change in gingival contour
5 Sulcular temperature change
6 Increased gingival exudate
7 Bleeding upon provocation
8 Absence of attachment loss“
9 Absence of bone loss*
10 Histological changes including an
inflammatory lesion
11 Reversible with plaque removal

13.  In 1965, Loe and associates demonstrated that in students with
clinically healthy gingivae, clinical symptoms of gingivitis
developed within 2 to 3 weeks if dental plaque was allowed to
accumulate freely.
 The thickness of the gingival plaque gradually increased during
the 3-week experimental period. For the first few days, this
plaque was composed of gram-positive cocci and rods,
representing the indigenous microflora of the tooth surface.
 After 4 to 5 days, filamentous organisms and gram-negative
cocci as well as rods "infected" the gingival plaque.
 Gradually, nonattaching spirochetes appeared in the gingival
sulcus, while the assortment of microorganisms in the gingival

15.  The pathogenesis of human periodontitis was first
documented in detail by Page and Schroeder in
1976 in an article that became a citation classic.
 The sequence of events cumulating in clinically
apparent gingivitis is categorized into initial, early,
and established stages, with periodontitis
designated as the advanced stage. One stage
evolves into the next, with no clear-cut dividing
lines.
 Initial,
 Early,
 Established,

17.  The initial lesion occurs within 2 to 4 days of free plaque
accumulation and
 The early lesion within 4 to 14 days. Both lesions represent
relatively acute stages of gingivitis and are the histologic
precursors of the established lesion in adults.
 In children, however, the ''early lesion" may persist for
prolonged periods.

18.  The first manifestations of gingival inflammation are
vascular changes consisting of dilated capillaries and
increased blood flow.
 Clinically, this initial response of the gingiva to bacterial
plaque (subclinical gingivitis) is not apparent.
 The mildest form represents the first line of nonspecific
defense: migration of PMNLs, through intact junctional
epithelium, to phagocytose and "kill" the bacteria in the
gingival crevice.

19.  There are, however, several mechanisms in the vicinity of the
teeth to fend off microbial infection and prevent the
development of periodontitis.
 The intact epithelial barrier
 Salivary secretions
 The gingival crevicular fluid (GCF) continuously flushes
the sulcus or pocket and delivers all the components of
blood serum, including complement proteins and specific
antibodies,
 In inflamed gingiva, the amount of GCF per site is
estimated to about 20 µl. A large population of B
lymphocyte cells and plasma cells accumulate.
 High turnover of both the epithelium and the components
of the extracellular matrix

20.  As long ago as the late 1960s, Waerhaug, the founding father
of modern periodontology, explained the important role of the
phagocytosing PMNLs as the first line of nonspecific host
defense in the pathogenesis of periodontal disease.
 Chemotactic antigens and other products are released from
the gingival microflora, resulting in vasodilation and
extravascular migration of PMNLs.
 several periopathogenic bacteria have significant antiPMNL
virulence factors. P gingivalis and A actinomycetemcomitans
are leukoaggressive;

22.  The first manifestations of gingival inflammation are vascular
changes consisting of
 dilated capillaries and
 increased blood flow.
 These initial inflammatory changes occur in response to
microbial activation of resident leukocytes and the subsequent
stimulation of endothelial cells.

23.  Subtle changes can also be detected in the junctional
epithelium and perivascular connective tissue at this early
stage. For example,
 the perivascular connective tissue matrix becomes altered,
and
 there is exudation and deposition of fibrin in the affected
area. Also,
 lymphocytes soon begin to accumulate.
 The increase in the migration of leukocytes and their
accumulation within the gingival sulcus may be correlated
with an increase in the flow of gingival fluid into the
sulcus.
 The character and intensity of the host response determine
whether this initial lesion resolves rapidly.

24.  Microscopically, some classic features of acute
inflammation can be seen in the connective tissue
beneath the junctional epithelium.
 Changes in blood vessel morphologic features
 widening of small capillaries or venules and
 adherence of neutrophils to vessel walls (margination) occur
within 1 week and sometimes as early as 2 days after plaque
has been allowed to accumulate.
 polymorphonuclear neutrophils (PMNs), leave the capillaries
by migrating through the walls (diapedesis, emigration).
 They can be seen in increased quantities in the connective
tissue, the junctional epithelium, and the gingival sulcus.

25.  The early lesion evolves from the initial lesion within about 1
week after the beginning of plaque accumulation.
 Clinical signs of erythema may appear, mainly because of the
proliferation of capillaries and increased formation of
capillary loops between rete pegs or ridges,
 bleeding on probing may also be evident.
 Gingival fluid flow and the numbers of transmigrating
leukocytes reach their maximum between 6 and 12 days
after the onset of clinical gingivitis.

26.  Heavier Plaque accumulation
 Transmigration of PMNs across
JE
 Early infiltration of Lymphocytes
observed
The amount of collagen destruction increases. 70% of the
collagen is destroyed around the cellular infiltrate.
The main fiber groups affected appear to be the circular and
dentogingival fiber assemblies.

27.  Fibroblasts show cytotoxic alterations, with a decreased
capacity for collagen production.
 Microscopic examination of the gingiva reveals
 a leukocyte infiltration in the connective tissue beneath the
junctional epithelium, consisting mainly of lymphocytes (75%,
with the majority T cells),
 some migrating neutrophils, as well as macrophages, plasma
cells, and mast cells.
 All the changes seen in the initial lesion continue to intensify
with the early lesion. Junctional epithelium becomes densely
infiltrated with neutrophils, as does the gingival sulcus, and
the junctional epithelium may begin to show development of
rete pegs or ridges

28.  After increased gingival plaque accumulation and longterm exposure
(more than 2 to 3 weeks) to bacterial challenge, early acute gingival
inflammation is followed by established gingival inflammation.
 This is characterized at the cellular level by an accumulation of B
lymphocytes, T lymphocytes, plasma cells, and macrophages in the
inflamed gingival connective tissue.
 On the other hand, the number of fibroblasts is reduced. Destruction of
the collagen fibers and the extracellular matrix also occurs, as does an
increase in the volume of infiltrate in which blood vessels proliferate.
 Nonspecific line of defense is now reinforced by mobilization of the
specific host immune response, via antibodies produced by plasma cells,
and the specific cell-mediated immune response by T cells.
Pathogenesis

29.  Plasma cells dominate
 Homeostasis is disturbed
 Activated PMNs secrete
cytokines, leukotrienes &
MMPs
 Activated Fibroblasts
secrete MMPs & TIMPs
MCP : Monocyte Chemoattractant Protien,
MIP : Macrophage Inflammatory Protien
RANTES : Regulated on activation normal T cell expressed and secreted

30.  In chronic gingivitis, which occurs 2 to 3 weeks after the
beginning of plaque accumulation,
 the blood vessels become engorged and congested,
 venous return is impaired, and
 the blood flow becomes sluggish.
 The result is localized gingival anoxemia, which super
imposes a somewhat bluish hue on the reddened gingiva.
 Extravasation of erythrocytes into the connective tissue
and breakdown of hemoglobin into its component pigments
can also deepen the color of the chronically inflamed
gingiva.

31.  Epithelial attachment is apically
displaced
 No loss of CT attachment
 Dense Inflammatory infiltrate
into deeper structures

32.  The predominance of plasma cells is thought to be a
primary characteristic of the established lesion.
 However, several studies of human experimental gingivitis
have failed to demonstrate plasma cell predominance in
the affected connective tissues, including one study of 6
months duration. (seymour et. al. 1983)
 Increases in the proportions of plasma cells were evident
with long-standing gingivitis, but the time for the
development of the classic "established lesion" may exceed

33.  An inverse relationship appears to exist between the number of intact
collagen bundles and the number of inflammatory cells.
 Collagenolytic activity is increased in inflamed gingival tissue by the
enzyme collagenase.
 Enzyme histochemistry studies have shown that chronically inflamed
gingivae have elevated levels of acid and alkaline phosphatase, ß-
glucuronidase, |3-glucosidase, ß-galactosidase, esterases,
aminopeptidase and cytochrome oxidase.
 Neutral mucopolysaccharide levels are decreased, presumably as a
result of degradation of the ground substance.
 Established lesions of two types appear to exist;
 some remain stable and do not progress for months or
years, and
 others seem to become more active and to convert to

34.  In histologic sections, an intense, chronic inflammatory reaction is
observed.
 A key feature that differentiates the established lesion is the increased
number of plasma cells, which become the preponderant inflammatory cell
type.
 Plasma cells invade the connective tissue not only immediately below the
junctional epithelium, but also deep into the connective tissue, around
blood vessels, and between bundles of collagen fibers.
 The junctional epithelium reveals widened intercellular spaces filled
with granular cellular debris, including lysosomes derived from disrupted
neutrophils, lymphocytes, and monocytes.
 The junctional epithelium develops rete pegs or ridges that protrude into
the connective tissue, and the basal lamina is destroyed in some areas.
 In the connective tissue, collagen fibers are destroyed around the

35.  Extension of the lesion into alveolar bone characterizes a fourth
stage known as the advanced lesion or phase of periodontal
breakdown.
 Microscopically, there is
 fibrosis of the gingiva and
 widespread manifestations of inflammatory and
immunopathologic tissue damage.
 In general at this advanced stage, plasma cells continue to
dominate the connective tissues, and neutrophils continue to
dominate the junctional epithelium and gingival crevice.
 Gingivitis will progress to periodontitis only in individuals who
are susceptible. However, whether periodontitis can occur
without a precursor of gingivitis is not known at this time